Allelic polymorphisms in the transcriptional regulatory region of apolipoprotein E gene.
In this work, we explored the existence of genetic variants within the apolipoprotein E gene transcriptional regulatory region, using a denaturing gradient gel electrophoresis screening of a region comprising nucleotides -1017 to +406. Upon a population study, three new polymorphic sites (-491, -427 and -219) and two mutations were found. Functional effects of the polymorphisms, assayed by transient transfection and electrophoretic mobility shift assays in a human hepatoma cell line, showed that polymorphisms at sites -491 and -219 of the APOE promoter produce variations in the transcriptional activity of the gene, most probably through differential binding of nuclear proteins.
Artiga
M J
MJ
Departamento de Biología Molecular, (C.S.I.C.-U.A.M.), Universidad Autónoma de Madrid, Cantoblanco, Spain.
Bullido
M J
MJ
Sastre
I
I
Recuero
M
M
García
M A
MA
Aldudo
J
J
Vázquez
J
J
Valdivieso
F
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004591:Electrophoresis, Polyacrylamide Gel; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007223:Infant; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D001057:Apolipoproteins E; D009687:Nuclear Proteins